Title: Joint Meeting of the Anti-Infective Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Open Public Meeting December 14-15, 2006
1Joint Meeting of the Anti-Infective Drugs
Advisory Committee and the Drug Safety and Risk
Management Advisory CommitteeOpen Public
MeetingDecember 14-15, 2006
- Prabhavathi Fernandes, Ph.D.
- President and CEO
- Cempra Pharmaceuticals, Inc.
- prabha_at_fernandes-domain.com
2All of Us Have the Same Goals
We all want affordable antibiotics -that are safe
and effective against resistant bacteria
Patients
Physicians
Pharma Biotech
FDA
Success REQUIRES that we are all on the same
tablet !
3The Tablet is Broken
Lack of clear guidelines to develop
antibacterials makes the financial risk too high
Pharma Biotech
The return on investment is too low
Patients
There are not enough safe and effective
antibiotics
FDA
We need extraordinarily safe antibiotics that
are more effective than placebo
Physicians
4Using Ketek as an Example - Find the Cause of
the Problem
Antibiotics developed used for serious
infections
Antibiotics safe effective
Patients demand for antibiotics for simple
infections
Pharma Success
1975
1940
FDA, patients Congress question use and safety
of antibiotics
Physician Patient comfort
WHERE ARE THE MAGIC BULLETS?
Increased profits from antibiotic sales for
simple infections
2005
1985
Millions of patients exposed
Increased patient exposure increased reporting
of adverse effects
Risk-Benefit?
Patient demand and pharma greed for drugs for
simple infections
Pharma markets aggressively for simple infections
5Thoughts that Have Arisen After Ketek was
Approved
- Should wide-spread use be discouraged to prevent
selection of resistant bacteria? - We are killing the goose that is laying the
golden eggs - Should FDA protect public from unnecessary
exposure to antibiotics that can result in harm? - Should patients be using so many antibiotics for
simple infections? - Should physicians be writing so many antibiotic
prescriptions? - Should pharma sales reps promote antibiotics for
simple infections?
6Unrealistic Expectations
- No drug (or antibiotic) is completely safe
- Risk-benefit analysis is easier when treating
serious infections - It is impossible to detect every rare side effect
in any-size trials- no point in increasing the
clinical trial size - Need pre-clinical toxicology, clinical safety in
1000 patients - Need mandatory submission of Phase IV data
- Ban on promotion for simple infections
- Waiting to get sufficient patients with resistant
bacterial infections to prove efficacy in
clinical trials is like waiting until a house is
on fire to buy insurance!
7Proposal for Clinical Trial Design to
Demonstrate Efficacy
- For simple infections, placebo controlled trials
are the only way to demonstrate that a drug is
effective - Comparator controlled trials should be used for
serious or complicated infections to demonstrate
efficacy - 200 cases tested with new drug vs. one of the TOP
two standard-of-care antibiotics - Non inferiority to these compounds should be
approved - Approval for organ system of infection (e.g.
Respiratory, SSSI) - In infectious diseases, the biomarker is
isolation of the pathogen demonstrate the
pathogen and clearance - A new antibiotic that has activity in vitro and
in animal model against resistant bacteria, and
has equal or even less activity as comparator
antibiotics in clinical trials, should be
approved for treating resistant bacteria
8Encouragement for Developing New Antibiotics
- Clear FDA guidelines to make drug development
feasible - Two adequate (400 patients each) and comparator
controlled, non-inferiority studies for serious
infections - Approval on the ORGAN SYSTEM basis to decrease
costs of multiple clinical trials - Some diseases are rare (e.g. endocarditis) and
guidelines could combine many rare, deep
tissue/organ infections into one claim - Government should provide incentives to small
companies who are addressing public health needs
for new antibiotics eg. matching grants,
development expense refunds, tax incentives etc.